Modulation of ventricular spiral-wave reentry by cardiac ion channel blockade

人们普遍认为功能性折返在室性心动过速/室颤(VT/VF)的发生和维持中起着重要作用。前导圈、各向异性折返和螺旋型兴奋等概念已被提出用于解释心脏功能性折返，但其确切机制尚不清楚。我们用高分辨率光学标测技术研究了室性心动过速的动力学和药物调控。通过冷冻消融左心室内膜侧，制作了兰根多夫灌流的兔心脏心外膜下二维心肌片(厚度约1 mm)。心脏用2μM的di-4-ANEPPS染色，用高速摄像机(时间分辨率为~1.3ms，空间分辨率为~0.1 mm)获取心肌的荧光图像。交叉场刺激诱发的室性心动过速往往是单次折返绕“Z”型传导阻滞功能线的结果。The Cen…与心肌纤维方向无关的阻滞线上更多的Tral节段与动作电位的突然相移有关。中央阻滞线出现无舒张期的小幅度双电位，提示存在“先导圆”型电张力相互作用。这两个末端段是由旋转枢轴点周围的局部传导延迟引起的，且这些线始终平行于心肌纤维方向。波前曲率和组织各向异性所造成的源汇不平衡可能是枢轴涂料周围局部传导延迟的原因。用匹西卡胺、异丙基吡胺和西比林阻断Na~+通道，可使局部传导延迟增加，延长终末阻滞线，除枢点周围外，还可引起明显的电舒缩(可兴奋间隙)。这些结果表明，二维心肌的功能性折返是由波前-波尾相互作用和由波前曲率和组织各向异性引起的源汇失衡决定的。较少

It is widely accepted that functional reentry plays an important role in the initiation and maintenance of ventricular tachycardia/fibrillation (VT/VF). Various concepts including "leading circle", anisotropic reentry and spiral-type excitation have been proposed to explain the functional reentry in the heart but its precise mechanisms remain to be elucidated. We investigated dynamics and pharmacological modulation cf VT by high-resolution optical mapping. Two-dimensional subepicardial ventricular myocardial sheet (〜1 mm in thickness) of the Langendorff-perfused rabbit heart was made by cryoablation of the endocardial side of the left ventricle. The heart was stained with di-4-ANEPPS (2 μM), and fluorescence images of theventricular myocardium were obtained via a high-speed video camera (temporal and spatial resolutions of〜1.3 ms and 〜0.1 mm, respectively). VT induced by cross-field stimulation was often the result of single reentry around a "Z"-shaped functional line of block. The cen … More tral segment of the block line, which was independent of the myocardial fiber direction, was associated with an abrupt phase-shift of the action potential. Small amplitude double potentials without electrical diastole were obtained at the central block line suggesting "leading circle"-type electrotonic interaction. The two terminal segments were caused by localized conduction delay around pivot points of the rotation and these lines were always parallel to the myocardial fiber direction. Source-to-sink imbalance created by wavefront curvature combined with tissue anisotropy may be responsible for the localized conduction delay around the pivot paints. Blockade of Na^+ channels by pilsicainide, disopyramide and cibenzoline extended the terminal block lines through the enhancement of the localized local conduction delay and caused appreciable electrical diastole (excitable gap) in the circuit except around pivot points. These results suggest that functional reentry in the two-dimensional ventricular myocardium is determined by wavefront-tail interaction and source-sink imbalance caused by wavefront curvature and tissue anisotropy. Less